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Updated: May 31, 2026
Murine Prostate Micro-dissection and Surgical Castration
Published on: May 11, 2016
Altered prostate epithelial development in mice lacking the androgen receptor in stromal fibroblasts
Shengqiang Yu1, Chiuan-Ren Yeh, Yuanjie Niu
1George Whipple Lab for Cancer Research, Departments of Pathology and Urology, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York 14642, USA.
Background:
Androgens and the androgen receptor (AR) play important roles in the development of male urogenital organs. We previously found that mice with total AR knockout (ARKO) and epithelial ARKO failed to develop normal prostate with loss of differentiation. We have recently knocked out AR gene in smooth muscle cells and found the reduced luminal infolding and IGF-1 production in the mouse prostate. However, AR roles of stromal fibroblasts in prostate development remain unclear.
Methods:
To further probe the stromal fibroblast AR roles in prostate development, we generated tissue-selective knockout mice with the AR gene deleted in stromal fibroblasts (FSP-ARKO). We also used primary culture stromal cells to confirm the in vivo data and investigate mechanisms related to prostate development.
Results:
The results showed cellular alterations in the FSP-ARKO mouse prostate with decreased epithelial proliferation, increased apoptosis, and decreased collagen composition. Further mechanistic studies demonstrated that FSP-ARKO mice have defects in the expression of prostate stromal growth factors. To further confirm these in vivo findings, we prepared primary cultured mouse prostate stromal cells and found knocking down the stromal AR could result in growth retardation of prostate stromal cells and co-cultured prostate epithelial cells, as well as decrease of some stromal growth factors.
Conclusions:
Our FSP-ARKO mice not only provide the first in vivo evidence in Cre-loxP knockout system for the requirement of stromal fibroblast AR to maintain the normal development of the prostate, but may also suggest the selective knockdown of stromal AR might become a potential therapeutic approach to battle prostate hyperplasia and cancer.
Insights
Androgen receptor (AR) in prostate stromal fibroblasts is essential for normal prostate development. Targeting stromal AR may offer new treatments for prostate hyperplasia and cancer.
Area of Science:
- Reproductive biology
- Molecular endocrinology
- Developmental biology
Background:
- Androgens and the androgen receptor (AR) are crucial for male urogenital development.
- Previous studies showed AR knockout in epithelium and smooth muscle impacts prostate development.
- The role of AR in prostate stromal fibroblasts remained undetermined.
Purpose of the Study:
- To investigate the specific role of the androgen receptor (AR) in prostate stromal fibroblasts during prostate development.
- To elucidate the mechanisms by which stromal AR influences prostate morphogenesis.
Main Methods:
- Generation of a tissue-specific knockout mouse model with AR deleted in stromal fibroblasts (FSP-ARKO).
- Utilized primary cultured prostate stromal cells for in vitro validation.
- Analyzed cellular proliferation, apoptosis, collagen composition, and growth factor expression.
Main Results:
- FSP-ARKO mice exhibited prostate cellular alterations, including reduced epithelial proliferation and increased apoptosis.
- Decreased collagen composition was observed in FSP-ARKO mouse prostates.
- In vitro studies confirmed that reduced stromal AR leads to impaired stromal and epithelial cell growth and decreased growth factor production.
Conclusions:
- This study provides the first in vivo evidence for the necessity of stromal fibroblast AR in maintaining normal prostate development.
- The findings suggest that selective knockdown of stromal AR could be a potential therapeutic strategy for prostate hyperplasia and cancer.
